One of the major problems observed in patients maintained on dialysis is the growing degree of humoral sensitization that precludes them from receiving a renal transplant. In 1973, the percentage of patients with lymphocytotoxic antibodies among our 200 prospective recipients was 32%. This has increased progressively to 95% in 1980. In 161 patients screened in September 1982, it was found that less than 5% had no antibodies to a 40-member peripheral blood lymphocyte (PBL) cell panel, 105 patients exhibited greater than 50% and 61 patients exhibited greater than 90% sensitization to the PBL cell panel. This increase in sensitization status of our patients has contributed to the declining transplantability of prospective kidney transplant recipients in our center. It is likely that the increasing degree of sensitization, also observed nationwide, is contributory to the decline in the transplant rate as a function of the percentage of the total dialysis population. This percentage has dropped from 60% in 1971 to 10% in 1977. The overall objective of the proposed project is to immunologically pre-condition highly sensitized prospective recipients so that they can be transplanted without the undue risks of accelerated rejection. In a controlled study, pre-conditioning will be attempted in 50 patients who exhibit greater than 50% humoral sensitization to the the PBL cell panel. Additional criteria for inclusion into this study will include persistance of antibodies at greater than 50% level over a period of 6 months and an inability to receive a transplant due to a positive T cell crossmatch against a minimum of 10 potential donors during the same period. The patients will be randomly assigned to either plasmapheresis or leuka-plasmapheresis treatment groups. Apheresis will be done 3 times weekly for a total of 9 procedures over a 3-week period. Each patient's estimated plasma volume will be exchanged during each plasmapheresis and 2x10 to the ninth - 5x10 to the ninth cells will be removed during each leukaplasmapheresis. The possibility that depletion of cytotoxic antibodies by plasmapheresis or depletion of cells and antibodies by leukaplasmapheresis will permit successful renal transplantation will be examined. Apheresis induced immune alterations including changes in sensitization status and changes in well-defined T and B cell functions will be investigated.